US 2003/119817 (A. Mehta) describes a series of substituted phenyl oxazolidinone compounds which are claimed to be useful in the treatment of microbial infection. WO 99/37304 (Rhone-Poulenc Rorer Pharmaceuticals Inc) and WO 01/07436 (Aventis Pharmaceuticals Products Inc) both describe a series of substituted oxoazaheterocyclyl Factor Xa inhibitors. WO 2002/79753 (Lion Bioscience AG) describes a series of 2-aminobenzoxazole derivatives which are claimed to be useful in the treatment of melanocortin receptor associated conditions e.g. inflammation. WO 2002/43762 and WO 00/59510 (Pfizer Prod Inc) both describe a series of heterocyclyl substituted pyrimidine derivatives which are claimed to be useful in the treatment of diabetes. JO 4018-071-A (Sumitomo Seiyaku KK) describes a series of bis-piperidine derivatives which are claimed to be acetylcholine esterase inhibitors for the treatment of Alzheimer's disease.
The histamine H3 receptor is predominantly expressed in the mammalian central nervous system (CNS), with minimal expression in peripheral tissues except on some sympathetic nerves (Leurs et al., (1998), Trends Pharmacol. Sci. 19, 177-183). Activation of H3 receptors by selective agonists or histamine results in the inhibition of neurotransmitter release from a variety of different nerve populations, including histaminergic and cholinergic neurons (Schlicker et al., (1994), Fundam. Clin. Pharmacol. 8, 128-137). Additionally, in vitro and in vivo studies have shown that H3 antagonists can facilitate neurotransmitter release in brain areas such as the cerebral cortex and hippocampus, relevant to cognition (Onodera et al., (1998), In: The Histamine H3 receptor, ed Leurs and Timmerman, pp 255-267, Elsevier Science B.V.). Moreover, a number of reports in the literature have demonstrated the cognitive enhancing properties of H3 antagonists (e.g. thioperamide, clobenpropit, ciproxifan and GT-2331) in rodent models including the five choice task, object recognition, elevated plus maze, acquisition of novel task and passive avoidance (Giovanni et al., (1999), Behav. Brain Res. 104, 147-155). These data suggest that novel H3 antagonists and/or inverse agonists such as the current series could be useful for the treatment of cognitive impairments in neurological diseases such as Alzheimer's disease and related neurodegenerative disorders.